Disorder of Calcium Homeostasis

ECF Calcium concentration in the human

body is tightly regulated by the three organs
Skeleton,kidney, and intestine with direct or
indirect interaction ofwith PTH,PTHtP,vitamin
D and calcitonin
Calcium in serum exists as
50% Ionised (ca2+)
10% non-ionised or organic ions such as citrate and
phosphate
40% protein bound (especially Albumin)
A fall in pH of o.1 unit will cause an approximately o.1
mEq/L rise in the concentration of ionized Ca2+,since
hydrogen ions displace calcium from albumin .whereas
alkalosis decrease free calcium by enhancing the
binding of Calcium .
 There is no correction for this effect of pH in
the previous formula , which limits its
accuracy.
 Most chemical laboratories only measure total serum
serum Calcium level
50% of total Calcium is bound to organic ions such as
citrate or phosphate
and
to proteins, especially albumin
So,if the serum albumin level is reduced ,
total calcium concentrates should be ‘corrected’
by adjusting the value for calcium upwards by o.4mg/dl for
each o.5mg/dl reduction in albumin below 4 mg/dl
Differetial Diagnosis of disorder of calcium
metabolism usually requires measurement of
-calcium/phosphate
-Alkaline phosphate
-renal function
--sometimes 25 (OH)D
-PTH
Status with excess PTH may cause
Hypercalcemia whereas PTH depletion is
associated with hypocalcemia
Similar effect of PTHrT promotes
-bone resorption
-enhance renal resorption of calcium
-decrease renal tubular reabsorption of
phosphate
Vit D and its metabolites increase intestinal
nabsorption of calcium and cause bone
resorption .So excess vit D induce
hypercalcemia,
Calcitonin inhibit bone resorption ,but its
physiological role in protecting against
hyperclcemia in human is not proven.
Estimation of Free calcium
-In a critically ill patiet free calcium should be
assessed with acid – base disturbance
-In patient exposed to a large amount of citrated
blood
-In those with blood protein disorder
 Hypercalcemia
Hypercalcemia results from an alteration in the net fluxes of
calcium to and from four compartment
-the bone
-the gut
-the kidney
-serum binding proteins
Most commonly ,hypercalcemia is caused by net calcium
movement from the skeleton into the ECF through incrased
osteoclastic bone resorption –as in-------
hyperparathyroidism or excess PTHrT present in malignancy.
In both thiazide use and its genetic counterpart ,
Getelman’s Syndrome –renal calcium
excretion is decreased .
Causes of HYPERCALCEMIA
TABLE DAVIDSON 765
CLINICAL MENIFESTATION
HYPERCLCEMIA ADVERSELY AFFECTS THE FUNCTION OF
NEARLY ALL ORGAN SYSTEM
But in particular the kidney ,central nervous system,and
cardiovascular system
The clinical manifestation of hypercalaemia relate more
to the degree of hypercalcemia and rate of increase
than the underlying cause .
Hypercalcemia may be classified based on total serum
calcium concentration as follows
Mild –Ca concentration = 10.4-11.9 mg/dl
Moderate—Ca concentrstion =12-13.9
mg/dlsevere(Hypercalcemic crisis) – Ca
concentration = 14-15/dl
Sign and symptom and complication of
hypercalcemia

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Hypercalciuria induced by hypercalcemia cause
nephrogenic diabetes insipidus with polyuria
and polydipsia leading to ECFvolume depletion
-decreased glomerular filtration rate (GFR)
-further incrase in serum calcium level
Nephrolithiasis and nephrocalcinosis are
common complication of hypercalcemia
The classic symptoms are described by the udage
“bones , stones, and abdominal groans”
Hypertension is common in hyperparathyroidism
A family history of hypercalcemia raises the
possibility of FHH or MEN (men 1 and men 2 )
MEN 1 –werner’s syndrome
MEN2 –sipple’s syndrome have common
primary hyoerthyroidism
Excess circulating 1,25(OH)2 D –from various
causesalso contribute to excess bone
resorption .
Increased intestinal calcium absorption may lead
to the development of hypercalcemia,as in
-Vit D overdose
Or-milk alkali syndrome
In general ,the kidney does not contribute to hypercalcemia ;
rather , it defends against the development of hypercalcemia
.
Typically hypercalciuria precedes hypercalcemia
Excess calcium acts on the calcium receptor(CaSR) to promote
calcium excretion.
In rare cases ,the kidney actively contribute to the
development of hypercalcemia-
Renal calcium excretion is not elevated in Familial
HYPOCALCURIC Hypocalcemia(FHH) –because of defective
renal respose to calcium itself